During the last year the EM lab has collaborated with labs in CBER and CDER in studies related to product safety. A) The genomes of mammalian cells contain retroviral sequences although partical formation may not be occurring. In experiments designed to simulate the activation of latent virus, cells of monkey and mouse origin were treated for various times with agents which induce viral replication. Cultures were subsequently examined by TEM for the presence of retroviral particles. An increase in both C-type and A-type retroviruses was seen in the treated murine cells. (With A. Khan & J. Sears, CBER, DVP) B) Coronary damage has been observed following the use of a Type-III phosphodiesterase inhibitor. As part of studies on the mechanism of this pathology, tissue samples from rats exposed to a single s.c. injection of inhibitor were examined by TEM. EM evaluation revealed damage to endothelial and vascular smooth muscle cells in several organs. These findings suggest that endothelial cell injury plays a critical role in the pathologic process. (With Dr. J. Zhang, CDER, Div. Of Applied Pharmacology Research). The EM lab is also participating in a research project related to vaccine development with Dr. I. Berkower (CBER, DVP). The goal of these studies is to create novel hybrid structures of the HIV gp 120 envelope molecule which will self-assemble into multimeric particles thereby enhancing their abiltiy to induce protective antibodies. The assembly of the hybrids into stable multimeric particles is assessed by TEM using negative staining. The EM lab has entered into an InterAgency Agreement with the Cell Biology lab of NCI for the study of melanomas, melanocyte physiology, and melanocyte-keratinocyte interactions. (With V. Hearing & V. Virador)